(282) Aromatase Inhibitors and The Incidence of Parkinson's Disease: Population-Based Cohort Study

Friday, August 26, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 613

Presenting Author(s)

Fran�ois MONTASTRUC
– MD, PhD, CHU Toulouse - Service de pharmacologie, Toulouse, France

Co-Author(s)

Farzin Khosrow-Khavar, PhD
– Postdoctoral Fellow, McGill School of Population and Global Health, Montréal, Quebec, Canada
Laurent Azoulay, PhD
– Associate Professor, McGill University, Montreal, Quebec, Canada, QC, Canada
Jean-Louis Montrastruc
– Professor, Toulouse University Hospital, Toulouse, France, France
Christel Renoux, MD PhD
– Associate Professor, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada., Canada

Background: Aromatase inhibitors (AIs) and tamoxifen are recommended for treatment of hormone receptor-positive breast cancer for up to ten years. AIs inhibit the synthesis of estradiol in post-menopausal women. Depletion of estrogen levels by AIs may circumvent the potential neuroprotective effects of estrogen and thus may lead to an augmented risk of Parkinson’s disease (PD) in this population when compared with tamoxifen. To date, no observational studies have assessed the risk of PD for AIs when compared directly with tamoxifen.

Objectives: To examine risk of PD associated with AIs compared with tamoxifen in women diagnosed with breast cancer.

Methods: We used the United Kingdom Clinical Practice Research Datalink to assemble a cohort of women aged 50 or over newly diagnosed with breast cancer and newly treated with either AIs or tamoxifen between 1995 and 2017. Patients were followed one year after treatment initiation until first occurrence of an incident diagnosis of PD or censored upon death from any cause, date of transfer out of practice, or end of study period (December 31, 2018). A one-year lag period was implemented to account for latency and exclude prevalent cases. We used Cox proportional hazards models with inverse probability of treatment weights to estimate weighted hazard ratios (HR) and 95% confidence intervals (CI) of PD associated with AIs compared with tamoxifen and accounted for over 30 confounders including demographic variables, comorbidities, comedications, and markers of healthcare utilization. In secondary analyses we examined whether the risk varies with cumulative duration of use and type of AIs. Sensitivity analyses were conducted by extending the lag period to three years, using a stricter outcome definition, requiring four prescription within one year to define exposure, stratifying by calendar time of cohort entry, using inverse probability of censoring weights for mortality as competing risk, and using multiple imputation for missing data.

Results: The study population consisted of 30,140 women with non-metastatic breast cancer, of whom 13,838 initiated AIs and 16,302 initiated tamoxifen. Compared with tamoxifen, use of AIs, was not associated with an increased risk of PD (crude incidence rate 7.2 vs. 6.5 per 10,000 person-years, respectively; weighted HR 0.94, 95% CI: 0.60-1.47). The risk did not vary with duration of use and by type of AIs (anastrozole: HR 0.95, 95% CI 0.55-1.63; letrozole: HR 1.09, 95% CI 0.56-2.13). Results were consistent across sensitivity analyses.

Conclusions: In this population-based study, the use of AIs, in comparison with tamoxifen, was not associated with an increased risk of PD in women diagnosed with breast cancer.